The severity of the clinical manifestations of anaemia and haemolysis correspond with the genetic defect and the degree of impairment in alpha-globin synthesis.

Alpha-thalassaemia is found in malarial regions of the world (Mediterranean, South-east Asia, Indian sub-continent, Middle East, Sub-Saharan Africa) and should be suspected in patients with these ethnic backgrounds and with microcytosis and/or anaemia.

The vast majority of alpha-thalassaemia patients are clinically well and most are asymptomatic. Many patients with Hb H are also clinically well, but are at risk for: acute haemolytic episodes; aplastic crises; iron overload, even in the absence of chronic transfusions; hypersplenism; and endocrine disease.

Education is an important part of management and should cover both the risks of acute events and, in genetic counselling, the risks of conceiving a child with Hb H disease or the potentially devastating Hb Bart hydrops fetalis.

Acquired Hb H disease is rare and occurs in association with haematological disorders, most commonly in male patients with myelodysplastic syndrome.

Definition

Alpha-thalassaemia is a group of disorders of haemoglobin synthesis, caused by mutations or deletions in at least 1 of the 4 alpha-globin genes, leading to variably impaired alpha-globin chain production, with accumulation of the now excess and unpaired beta-globin chains. These defects lead to the corresponding clinical manifestations of anaemia and haemolysis of variable severity.
[1]Weatherall D. The molecular basis for phenotypic variability of the common thalassaemias. Mol Med Today. 1995;1:15-20.
http://www.ncbi.nlm.nih.gov/pubmed/9415132?tool=bestpractice.com
Normal human haemoglobin consists of a tetramer of 2 pairs of globin polypeptide chains, 1 pair of alpha-like chains and 1 pair of non-alpha chains, each of which contains a haem group. Two copies of the alpha-globin gene (designated alpha-2 and alpha-1) are located on each chromosome 16. The upstream regulatory element HS-40 controls alpha-globin expression.
[2]Ribeiro DM, Sonati MF. Regulation of human alpha-globin gene expression and alpha-thalassemia. Genet Mol Res. 2008;7:1045-1053.
http://www.funpecrp.com.br/gmr/year2008/vol7-4/pdf/gmr472.pdf
http://www.ncbi.nlm.nih.gov/pubmed/19048483?tool=bestpractice.com

Disclosures

Dr Janet L. Kwiatkowski would like to gratefully acknowledge Dr Elizabeth A. Price and Dr Stanley L. Schrier, the previous contributors to this monograph. EAP declares that she has no competing interests. SLS has received NIH research funds, has received funds for organizing an educational symposium, and is an author of a number of references cited in this monograph.